More than 30,000 people demonstrated in Bucharest and other major cities to demand a "profound change" in the government, AFP news agency reported.

Wednesday's turnout was even bigger than one the previous evening when some 20,000 demonstrators massed in Bucharest's Victory Square, the seat of government, calling for Ponta's resignation and that of his interior minister, Gabriel Oprea.

Protesters said the government's resignation should be just the beginning of reforming a political class and public administration widely seen as corrupt.

"We came here first of all to fight against corruption, people who are corrupt and the system which defends corrupt people. If the system doesn't remove corrupt people by itself, people will make their own justice. If in 1989 (anti-Communist revolution) people fought for liberty, in 2015 we are fighting for justice," said protester, Hans.

Protesters hold banners reading "Corruption kills" and "The Church washes brains and launders public money" during a rally in Bucharest [Vadim Ghirda/Associated Press]

"People want a change in the system, half measures will no longer work," Marius Matache, a musician taking part in the march, told AFP.

Ponta, prime minister since 2012, had been under pressure to quit weeks before the blaze, after going on trial in September on charges of fraud, tax evasion and money laundering. He is likely to face his first court hearings later in November.

His departure might lead to a political realignment, although the coalition of three mainly leftist parties that form a majority in parliament showed no signs of a split. A national election is due in December 2016.

But those on the streets said they wanted to see a completely new leadership.

"We want new people, at least a technocratic government. If there are no clean politicians at the moment, then let's have a technocratic government formed from the many specialised people we have in our country," said protester, Bogdan.

The marchers chanted "Ponta resign" and "Killers", and some waved the national flag with holes in it - a symbol of the popular revolution 25 years ago that toppled the dictator Nicolae Ceausescu.

"This tragedy touched the nation's most sensitive nerve," President Klaus Iohannis said. "Romanians' indignation has turned into a real revolt."

Thousands attend a rally in reaction to the nightclub fire accident at the University Plaza in Bucharest, Romania, late 04 November 2015. [EPA]